Neurogenic pulmonary edema (NPE) is a form of edema that may develop after CNS trauma that intensely activates the sympathetic nervous system (SNS). The long term objectives of this program are to determine the basic mechanisms by which such excessive SNS activity affects lung blood flow and fluid balance and how these mechanisms act in concert to product NPE. An understanding of these mechanisms is important for the design of effective preventive and treatment measures. This project is composed of 5 studies. Study 1 is designed to determine if the transient increase in venous return that occurs after massive SNS activation contributes to the pulmonary hypertension of NPE. This will be accomplished by comparing the degrees of pulmonary hypertension that develops after norepinephrine administration in the anesthetized dog under conditions where the venous return is either kept constant or allowed to increase. Study 2 is designed to determine how the pulmonary vascular macromolecular sieving capability is altered after injury by the high vascular pressures that occur in NPE. This will be accomplished by evaluating the ability of an in situ lung lobe preparation to sieve endogenous plasma proteins of varying molecular size before and after injury. Study 3 is designed to determine the relative contribution of extraalveolar vessel injury to the total vascular injury. This will be accomplished by determining how the filtration coefficients of arterial and venous extraalveolar vessel segments of an isolated perfused lung lobe preparation are altered by barotrauma. Study 4 is designed to determine the degree and time course of perfusion heterogeneity development in the lung after massive SNS activation. This will be accomplished by analyzing how the pulmonary vaScular and extravascular transport functions (determined by indicator dilution) change after SNS produced by intracisternal veratrine administration in the anesthetized dog. Study 5 is designed to determine if the perfusion heterogeneity is a consequence of the mechanical increases in pulmonary vascular pressure or results from other SNS- induced effects. This will be accomplished by comparing the pulmonary vascular and extravascular transport functions obtained from animals in which pulmonary vascular pressures are increased mechanically with those in which pressures are increased by SNS activation.
